Hypoxia-inducible MicroRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma

Authors

  • Qiao Ying,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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    • These authors contributed equally to this work.

  • Linhui Liang,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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    • These authors contributed equally to this work.

  • Weijie Guo,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Ruopeng Zha,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Qi Tian,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Shenglin Huang,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jian Yao,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jie Ding,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Meiyan Bao,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Chao Ge,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Ming Yao,

    1. Department of Experimental Pathology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jinjun Li,

    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Xianghuo He

    Corresponding author
    1. State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    • Professor, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No.25/Ln.2200, Xie Tu Road, Shanghai 200032, China
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    • fax: 86-21-64436539


  • Potential conflict of interest: Nothing to report.

  • This work was supported by grants from the National Natural Science foundation of China (81071637, to X.H; 91029728, to X.H; 81101587, to L.L), the Science and Technology Commission of Shanghai Municipality (10JC1414200, to X.H; 11XD1404500, to X.H), the Shanghai Municipal Bureau of Public Health (2007088, to L.L), and the Shanghai Rising-star Program Funds (11QA1406200, to L.L).

Abstract

As the “master” microRNA that is induced by hypoxia, miR-210 is involved in multiple processes in the hypoxia pathway. However, whether miR-210 mediates hypoxia-induced tumor cell metastasis still remains unclear. Here, we demonstrate that miR-210 is frequently up-regulated in hepatocellular carcinoma (HCC) samples and promotes the migration and invasion of HCC cells. Furthermore, miR-210 can be induced by hypoxia in HCC cells and mediates hypoxia-induced HCC cell metastasis. We identify vacuole membrane protein 1 (VMP1) as the direct and functional downstream target of miR-210; in addition, we show that its expression is negatively correlated with the expression of miR-210 in HCC. Intriguingly, VMP1 is reduced by hypoxia, and down-regulation of VMP1 by miR-210 mediates hypoxia-induced HCC cell metastasis. Conclusion: These findings extend our understanding of the function of miR-210 in the hypoxia pathway, and this newly identified hypoxia/miR-210/VMP1 pathway should facilitate the development of novel therapeutics against hypoxic tumor cells. (HEPATOLOGY 2011)

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